沃戈宁通过LSD1-p65轴调节巨细胞极化和炎症信号,以缓解骨关节炎
Zhe Cai1, Chengyu Lu2, Dehui Chen2
1Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, 510623, China; Department of Allergy, Immunology and Rheumatology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, 510623, China.
概括
沃贡尼是一种天然化合物,通过通过LSD1-p65轴调节巨细胞极化和炎症途径来治疗关节炎症 (OA),促进关节的修复.
科学领域:
- 生物化学 生物化学
- 免疫学 免疫学 免疫学
- 药理学 药理学是指药理学的学科.
背景情况:
- 骨关节炎 (OA) 是一种由炎症和软骨退化为特征的退行性关节疾病.
- 介质阴茎不稳定 (DMM) 是一种常见的模型,用于诱导研究环境中的OA.
- 了解OA病原体背后的分子机制对于开发有效治疗方法至关重要.
研究的目的:
- 在DMM诱导的OA小鼠模型中阐明wogonin的治疗机制.
- 为了研究沃贡因对巨细胞两极分化和炎症信号传递的影响.
- 确定OA中由沃贡因调节的特定分子标和途径.
主要方法:
- 一个DMM诱导的OA小鼠模型被用关节内Wogonin注射治疗.
- 在体外研究中使用LPS刺激的巨细胞,骨质母细胞和初级红细胞.
- 技术包括免疫组织化学,RNA-seq,CRISPR基因编辑,分子对接和DARTS测试.
主要成果:
- 沃戈宁向氨酸特异性基因组脱甲酶1A (LSD1/KDM1A),抑制M1巨细胞极化并促进M2极化.
- 沃戈宁通过破坏LSD1-介导的p65脱甲基化和恢复自来抑制JNK/NF-κB通路.
- 在体内,沃戈宁改善了软骨完整性,减少了炎症 (IL-6),并稳定了下骨.
结论:
- 沃戈宁通过准LSD1-p65轴,重新平衡巨细胞两极分化,减轻炎症来缓解OA病理.
- 沃贡尼显示出免疫反应和组织修复的双重调节,突出显示其作为疾病修饰性OA药物的潜力.
- 需要在大型动物模型和人体组织中进一步验证临床转化.
相关概念视频
01:20The JAK-STAT Signaling Pathway
9.2K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
9.2K
02:26NF-κB-dependent Signaling Pathway
7.8K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
7.8K
01:28Inflammatory Response
7.2K
An inflammatory response is a localized, nonspecific immune reaction that occurs when a tissue is injured. It is characterized by redness, swelling, heat, and pain, which are commonly called the cardinal signs and symptoms of inflammation. Inflammation can sometimes result in a loss of function.
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
7.2K
01:31Osteoclasts in Bone Remodeling
3.2K
Osteoclasts are cells responsible for bone resorption and remodeling. They originate from hematopoietic progenitor cells present in the bone marrow. Numerous progenitor cells fuse to form multinucleated cells, each with 10-20 nuclei. A single osteoclast has a diameter of 150 to 200 µM. These cells have ruffled borders that break down the underlying bone tissue and release minerals such as calcium into the blood in bone resorption. Osteoclasts cling to bones with their ruffled edges during...
3.2K